绝经后骨质疏松（PMOP）是发病率最高的原发性骨质疏松症，已列入国家重点攻关的老年三大疾病之一。临床常用化学药物不良反应严重，长期使用受限。我们前期发现女贞子-墨旱莲配伍具有抗PMOP作用，长期应用无雌激素样副作用。二者配伍防治PMOP的物质基础及分子机制有待阐明。鉴于代谢组学和血清药物化学在中药物质基础研究方面的优势互补，本项目通过代谢组学以内源性代谢标识物网络修复为指标发现活性部位，揭示活性部位在PMOP模型大鼠中的血清药物化学特征，通过相关性分析发现药效物质群，进一步采用体内外模型比较药效物质群潜在化学成分及其配伍的抗骨质疏松作用以阐明物质基础，探讨其通过PMOP病理过程的最终通路——RANK通路抑制骨吸收的分子机制。本课题将阐明女贞子-墨旱莲防治PMOP的科学内涵，为创制安全有效、长期应用的现代中药制剂治疗PMOP提供实验依据，为开拓中药物质基础的研究思路提供借鉴

Postmenopausal osteoporosis (PMOP) is the highest incidence of primary osteoporosis, and it has been included in national three age-related diseases. Commonly used chemical drugs have serious adverse reactions, so long-term use is limited. In our previous study, Lucidum-Eclipta compatibility performed excellent anti-PMOP effect, and increased the ratio of OPG / RANKL protein expression in rat femur tissue, but estrogen-like side effects were not observed with long-term use. However, the material basis and in-depth molecular mechanism remain to be further clarified. The present project, under the guidance of the core concept of Traditional Chinese Medicine "holistic view" and “Differential Treatment”, will ① clarify the anti-PMOP material basis of Ligustrum - Eclipta using metabolomics and serum drug research ideas and PMOP rat model; ② explore its molecular mechanism by RANK pathway. The project will not only clarify the scientific connotation of Ligustrum-Eclipta compatibility to anti-PMOP, but also has important value in creating an effective, long-term applicated modern Chinese medicine preparation.

发现旱墨莲中有效成分刺囊酸具有显著的对抗大鼠卵巢摘除引起的骨质疏松。刺囊酸是一种天然的三萜类化合物，富含于多种草药中，并已经在中国有多种药用用途。在本研究中，我们首次系统地研究了刺囊酸对去卵巢大鼠骨质疏松症的影响。三个月龄雌性去势（OVX）SD大鼠用于评价刺囊酸的骨保护作用。结果表明，刺囊酸（5或15mg/kg/day）12周，防止OVX引起的低水平的最大应力和股骨弹性模量。刺囊酸也恢复在去卵巢大鼠骨代谢标志物水平，包括骨钙素、碱性磷酸酶、钙、磷和尿脱氧吡啶啉。刺囊酸可以防止在卵巢切除所引起的股骨总骨密度的变化。然而，只有高剂量（15mg/kg/day）刺囊酸明显改善骨小梁结构，增加骨体积/组织体积，骨小梁数量和厚度。此外，刺囊酸治疗降低OVX大鼠血清IL-1β和TNF-α的含量。总之，刺囊酸可以防止去卵巢大鼠骨量和骨强度降低，改善松质骨结构和生化性质。因此，刺囊酸可以作为一个新的候选药物或一个抗骨质疏松症的先导化合物，开发新型治疗药物。此外，采用体内外模型评价单体及配伍的抗骨质疏松 作用，进行女贞子-墨旱莲防治骨质疏松 的物质基础研究，希望发现协同作用的药效物质基础。研究结果以第一作者发表于PloS ONE 2015。